TR&D 4: Optical Imaging & Monitoring P.I: Arjun G. Yodh, PhD ABSTRACT Diffuse optics has proven to be clinically relevant, and as a result, many scientists, engineers and clinicians are now working together in this field of biomedicine. Technological innovation with diffuse optics continues along two branches: imaging and monitoring. Clinical innovation with diffuse optics is focused on many problems, notably cancer diagnosis and monitoring and brain injury management. Biomarkers are the key reason for the sustained interest of this broad community. In particular, hemodynamic, perfusion and metabolic contrasts, among others, are available to the optical method and have demonstrated value for detection, diagnosis and monitoring of tumors, and for characterization and monitoring of diseased and injured states of brain and muscle tissue. The technology is also attractive because it offers the possibility for non-invasive, rapid, portable and continuous measurements at the bedside. TRD4 will focus on both branches of technology development, imaging and monitoring, and it will also focus on two important classes of clinical problem, breast cancer and brain injury. A recurring theme is the combination of two data-types: blood flow & oxy-/deoxy- hemoglobin concentration. In combination, these data provide untapped access to tissue metabolism and autoregulation. One research direction is oriented towards neurovascular monitoring. TRD4 will develop new dual-data- type instrumentation and algorithms based on blood flow and blood oxygenation contrast that directly address issues that have plagued all optical measurements of brain: corrupting signals from extra-cerebral tissues, and the so-called ?hair? problem. Solution of these problems leads naturally to the development of a more comprehensive optical monitor that interrogates cortical flow and oxygenation comprehensively (and non- invasively) over the whole head. Lastly, minimally-invasive probes for spinal cord monitoring will be developed to address a new clinical application in the surgical suite wherein continuous, real-time measurements at the surgical bedside are crucial: spinal cord ischemia. The second research direction is oriented towards breast cancer imaging. TRD4 will complete and utilize a multi-modal DOT-MRI clinical breast imager within a standard-of-care hospital MRI scanner at the Hospital of the University of Pennsylvania (i.e., 1.5 T with Sentinelle breast biopsy coils). Soft spatial priors from MRI enable tumor optical properties to be derived with high fidelity, and the combination of optical and MRI biomarkers will be explored for improved cancer characterization via computer aided diagnosis (CAD). Finally, multi-modal experiments will combine DOT hemoglobin concentration data with Ktrans data (i.e., flow data) from dynamic contrast enhanced MRI (DCE-MRI) and KWIC (TRD 3) to enable construction of oxygen metabolism images of breast.